The glycoprotein fibronectin is usually decreased on tumor cells and is involved in cell adhesion and migration. Fibronectin was present immunologically throughout the animal kingdom, but not in bacteria or plants. Its widespread distribution and conservation suggests its importance, e.g., in cell interactions. The structure of fibronectin was analyzed by a novel surface chemistry approach. Its molecular area was regulated by ionic strength and pH, and calcium ions were essential for maintaining its conformation. These results indicate the importance of ionic and divalent cation-mediated interactions in the structure of this glycoprotein. A dualistic nature of fibronectin in its function as an adhesion protein was discovered. Although it mediated cell adhesion when attached to substrates, fibronectin became an auto-inhibitor of its own function when present at high concentrations in solution. This activity was retained in fragments and even in synthetic peptides. These results suggest that an adhesion protein can be a positive or negative effector depending on its location and concentration, and that the recognition of this glycoprotein may depend on a small peptide sequence. Binding of fibronectin to the cell surface appears to be specific and of moderate affinity. Possible integral membrane protein receptors for fibronectin, especially a 140K protein complex, are being characterized; monoclonal antibodies to the latter antigen inhibited fibronectin-mediated adhesion. In collaborative experiments, the cell surface receptor for insulin was found to be synthesized as a single pro-receptor precursor, then cleaved to form its subunits. Our future objectives will be to use peptide mapping, immunological criteria, and sequencing of recombinant DNA clones to determine the relatedness of fibronectins, to use synthetic peptides to probe the role of fibronectin in vivo and the function of its putative recognition sequence in vitro, and to identify its receptor using monoclonal antibodies and reconstitution assays.